Douros 2019 JCI Insight

Douros JD, Niu J, Sdao SM, Gregg T, Fisher-Wellman KH, Bharadwaj MS, Molina A, Arumugam R, Martin MD, Petretto E, Merrins MJ, Herman MA, Tong J, Campbell JE, D'Alessio D (2019) Sleeve gastrectomy rapidly enhances islet function independently of body weight. JCI Insight 4:126688.

» PMID: 30777938 Open Access

Douros JD, Niu J, Sdao SM, Gregg T, Fisher-Wellman KH, Bharadwaj MS, Molina A, Arumugam R, Martin MD, Petretto E, Merrins MJ, Herman MA, Tong J, Campbell JE, D'Alessio D (2019) JCI Insight

Abstract: Bariatric surgeries including vertical sleeve gastrectomy (VSG) ameliorate obesity and diabetes. Weight-loss and accompanying increases to insulin sensitivity contribute to improved glycemia after surgery, however, studies in humans also suggest weight-independent actions of bariatric procedures to lower blood glucose, possibly by improving insulin secretion. To evaluate this hypothesis, we compared VSG operated mice with pair-fed, sham-surgical controls (PF-Sham) 2 weeks after surgery. This paradigm yielded similar post-operative body weight and insulin sensitivity between VSG and calorically restricted PF-Sham animals. However, VSG improved glucose tolerance and markedly enhanced insulin secretion during oral nutrient and intraperitoneal glucose challenges compared to controls. Islets from VSG mice displayed a unique transcriptional signature enriched for genes involved in Ca²⁺ signaling and insulin secretion pathways. This finding suggests that bariatric surgery leads to intrinsic changes within the islet that alter function. Indeed, islets isolated from VSG mice had increased glucose-stimulated insulin secretion and a left-shifted glucose sensitivity curve compared to islets from PF-Sham mice. Isolated islets from VSG animals showed corresponding increases in the pulse duration of glucose-stimulated Ca²⁺ oscillations. Together these findings demonstrate a weight-independent improvement in glycemic control following VSG, which is, in part, driven by improved insulin secretion and associated with substantial changes in islet gene expression. These results support a model in which β-cells play a key role in the adaptation to bariatric surgery and the improved glucose tolerance that is typical of these procedures. • Keywords: Diabetes, Endocrinology, Glucose metabolism, Islet cells, Metabolism • Bioblast editor: Plangger M • O2k-Network Lab: US NC Winston-Salem Molina AJA

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes 

Organism: Mouse  Tissue;cell: Islet cell;pancreas;thymus  Preparation: Permeabilized tissue 

Regulation: ATP production  Coupling state: LEAK, OXPHOS, ET  Pathway: N, Gp, NS  HRR: Oxygraph-2k 

Labels, 2019-02